tbuckley/cabot-search huggingface dataset:
Predicting All-Cause Mortality in Women With and Without Breast Cancer Using the Schonberg Index: A Women’s Health Initiative Study
Authors: Rebecca A. Nelson, Enrique Soto-Perez-de-Celis, Rowan T. Chlebowski, Mara Schonberg, Joanne Mortimer, Kathy Pan, Lifang Hou, Marian L. Neuhouser, Kerryn W. Reding, Nazmus Saquib, Jean Wactawski-Wende, Emily Wolfson, Mina S. Sedrak, Laura Kruper
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: When treating older women with breast cancer, life expectancy is an important consideration. ASCO recommends calculating 10-year mortality probabilities to inform treatment decisions. One useful tool is the Schonberg index, which predicts risk-based all-cause 10-year mortality. We investigated the use of this index in women aged ≥65 years with breast cancer in the Women’s Health Initiative (WHI). Methods: We calculated 10-year mortality risk scores for 2,549 WHI participants with breast cancer (“cases”) and 2,549 age-matched breast cancer–free participants (“controls”) using Schonberg index risk scoring. Risk scores were grouped into quintiles for comparisons. Risk-stratified observed mortality rates and 95% confidence intervals were compared across cases and controls. Observed 10-year mortality rates in cases and controls were also compared with Schonberg index–based predicted 10-year mortality rates. Results: Compared with controls, cases were more often white ( P =.005), had higher income and education levels ( P &lt;.001 for both), more often lived with their husband/partner ( P &lt;.001), scored higher on subjective health/happiness ( P &lt;.001), and needed less assistance in activities of daily living ( P &lt;.001). Participants with breast cancer had similar risk-stratified 10-year mortality rates compared with controls (34% vs 33%, respectively). Stratified results showed that cases had slightly higher mortality rates than controls in the lowest risk quintile and lower mortality rates in the 2 highest risk quintiles. Observed mortality rates in cases and controls were similar to Schonberg index–predicted mortality, with model c-indexes of 0.71 and 0.76, respectively. Conclusions: Among women aged ≥65 years with incident breast cancer, the Schonberg index–based risk-stratified 10-year mortality rates were similar to those in women without breast cancer, demonstrating a similar performance of the index among both populations. Along with other health measures, prognostic indexes can help predict survival among older women with breast cancer and support geriatric oncology guidelines that promote using life expectancy calculation tools for shared decision-making.
Pathogenesis, Evaluation, and Management of Pulmonary Vein Stenosis
Authors: Trevor Simard, Dhruv Sarma, William R. Miranda, C. Charles Jain, Jason H. Anderson, Jeremy D. Collins, Abdallah El Sabbagh, Aravdeep Jhand, Tobias Peikert, Guy S. Reeder, Thomas M. Munger, Douglas L. Packer, David R. Holmes
Journal: Journal of the American College of Cardiology (2023)
Association of Beta-Blocker Therapy With Cardiovascular Outcomes in Patients With Stable Ischemic Heart Disease
Authors: Lucas C. Godoy, Michael E. Farkouh, Peter C. Austin, Baiju R. Shah, Feng Qiu, Cynthia A. Jackevicius, Harindra C. Wijeysundera, Harlan M. Krumholz, Dennis T. Ko
Journal: Journal of the American College of Cardiology (2023)
Refining Risk Stratification Among Children With Latent Rheumatic Heart Disease
Authors: Andrea Beaton, Emmy Okello, Joselyn Rwebembera, Anneke Grobler, Daniel Engelman, Juliet Alepere, Jonathan Carapetis, Alyssa DeWyer, Peter Lwabi, Mariana Mirabel, Ana Olga Mocumbi, Miriam Nakitto, Emma Ndagire, Maria Carmo P. Nunes, Isaac Otim Omara, Rachel Sarnacki, Amy Scheel, Nigel Wilson, Liesl Zühlke, Ganesan Karthikeyan, Craig A. Sable, Andrew C. Steer
Journal: Circulation (2023)
Reduced Stress-Related Neural Network Activity Mediates the Effect of Alcohol on Cardiovascular Risk
Authors: Kenechukwu Mezue, Michael T. Osborne, Shady Abohashem, Hadil Zureigat, Charbel Gharios, Simran S. Grewal, Azar Radfar, Alexander Cardeiro, Taimur Abbasi, Karmel W. Choi, Zahi A. Fayad, Jordan W. Smoller, Rachel Rosovsky, Lisa Shin, Roger Pitman, Ahmed Tawakol
Journal: Journal of the American College of Cardiology (2023)
The association between alcohol consumption and the risk of hepatocellular carcinoma according to glycemic status in Korea: A nationwide population-based study
Authors: Eun Ju Cho, Goh Eun Chung, Jeong-Ju Yoo, Yuri Cho, Dong Wook Shin, Yoon Jun Kim, Jung-Hwan Yoon, Kyungdo Han, Su Jong Yu
Journal: PLoS Medicine (2023)

Background Alcohol and diabetes are known risk factors for hepatocellular carcinoma (HCC); however, it is unclear whether the association between alcohol consumption and HCC risk differs by fasting serum glucose level and diabetes. We investigated the dose–response relationship between alcohol consumption and the risk of HCC according to glycemic status. Methods and findings This population-based observational cohort study included patients who underwent general health checkups in 2009 using the Korean National Health Insurance Service Database. The primary outcome was HCC incidence, and Cox proportional hazard regression analysis was performed to estimate the relationship between alcohol consumption and HCC risk according to glycemic status. A total of 34,321 patients newly diagnosed with HCC were observed in the median follow-up period of 8.3 years. In the multivariable model, we adjusted for age, sex, smoking, regular exercise, income, hypertension, dyslipidemia, and body mass index. Mild-to-moderate alcohol consumption increased the risk of HCC in all glycemic statuses (normoglycemia: hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.02 to 1.10; prediabetes: HR, 1.19; 95% CI, 1.14 to 1.24; and diabetes: HR, 2.02; 95% CI, 1.93 to 2.11) compared to normoglycemic nondrinking. Heavy alcohol consumption also increased the risk of HCC in all glycemic statuses (normoglycemia: HR, 1.39; 95% CI, 1.32 to 1.46; prediabetes: HR, 1.67; 95% CI, 1.58 to 1.77; and diabetes: HR, 3.29; 95% CI, 3.11 to 3.49) compared to normoglycemic nondrinking. Since alcohol consumption information in this study was based on a self-administered questionnaire, there may be a possibility of underestimation. Although we excluded patients with a history of viral hepatitis using diagnosis codes, we could not obtain information on hepatitis B or hepatitis C serum markers. Conclusions Both mild-to-moderate and heavy alcohol consumption was associated with an increased risk of HCC in all glycemic statuses. The increased risk of HCC according to alcohol consumption was the highest in the diabetes group, suggesting that more intensive alcohol abstinence is required for patients with diabetes.
Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme
Authors: Roy Fleischmann, Jeffrey R Curtis, Christina Charles-Schoeman, Eduardo Mysler, Kunihiro Yamaoka, Christophe Richez, Hannah Palac, Deanne Dilley, Jianzhong Liu, Sander Strengholt, Gerd Burmester
Journal: Annals of the Rheumatic Diseases (2023)

Increased risk of serious adverse events (AEs) was reported for tofacitinib relative to tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis (RA) aged ≥50 years enriched for cardiovascular (CV) risk (ORAL Surveillance). We assessed post hoc the potential risk of upadacitinib in a similar RA population.Pooled safety data from six phase III trials were evaluated post hoc for AEs in patients receiving upadacitinib 15 mg once a day (with or without conventional synthetic disease-modifying antirheumatic drugs), adalimumab 40 mg every other week with concomitant methotrexate (MTX), or MTX monotherapy in the overall trial population and in a subset of patients with higher CV risk (aged ≥50 years, ≥1 CV risk factor). Higher-risk patients from a head-to-head study of upadacitinib 15 mg versus adalimumab (SELECT-COMPARE) were assessed in parallel. Exposure-adjusted incidence rates for treatment-emergent AEs were summarised based on exposure to upadacitinib or comparators.A total of 3209 patients received upadacitinib 15 mg, 579 received adalimumab and 314 received MTX monotherapy; ~54% of the patients were included in the overall and SELECT-COMPARE higher-risk populations. Major adverse cardiovascular events (MACE), malignancy (excluding non-melanoma skin cancer (NMSC)) and venous thromboembolism (VTE) were more frequent in the higher-risk cohorts versus the overall population but were generally similar across treatment groups. Rates of serious infections in higher-risk populations and herpes zoster (HZ) and NMSC in all populations were higher with upadacitinib 15 mg than comparators.An increased risk of MACE, malignancy (excluding NMSC) and VTE was observed in higher-risk populations with RA, yet risk was comparable between upadacitinib-treated and adalimumab-treated patients. Higher rates of NMSC and HZ were observed with upadacitinib versus comparators across all populations, and increased rates of serious infections were detected in upadacitinib-treated patients at higher CV risk.NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847 and NCT03086343.
Correction to: 2023 EPI/Lifestyle Abstract 17
Journal: Circulation (2023)

a correction notice is needed.1.In the "Background" section, sentence 5, "Anonymized" was added before "mobile phone data can be…" 2.In the "Methods" section, the beginning of sentence 3 read, "Mobile phone location data from CUEBIQ were used to estimate racial/ethnic density…" It has been updated to read, "Aggregated and anonymized mobilephone data from opted-in devices were used to estimate racial/ethnic density…" 3.In the "Methods" section, sentence 4 read, "Racial and economic composition of the device was assigned by the user's estimated home census tract." It has been updated to read, "Racial and economic composition was assigned by the device's inferred home census tract." 4.At the end of the "Methods" section, a sentence was added: "At no point was mobility data linked to individual health records.
Retinal Nerve Fiber Layer Optical Texture Analysis
Authors: Clarice Kai-Ying Su, Philip Yawen Guo, Poemen Pui Man Chan, Alexander Ka-Ngai Lam, Christopher Kai Shun Leung
Journal: Ophthalmology (2023)

To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) to investigate the prevalence, patterns, and risk factors of RNFL defects in patients with ocular hypertension (OHT) who showed normal optic disc and RNFL configuration in clinical examination, normal RNFL thickness on OCT analysis, and normal visual field (VF) results.Cross-sectional study.Six hundred eyes of 306 patients with OHT.All participants underwent clinical examination of the optic disc and RNFL, OCT RNFL imaging, and 24-2 standard automated perimetry. To detect RNFL defects, ROTA was applied. The risk score for glaucoma development was calculated according to the Ocular Hypertension Treatment Study and European Glaucoma Prevention Study (OHTS-EGPS) risk prediction model. Risk factors associated with RNFL defects were analyzed using multilevel logistic regression analysis.Prevalence of RNFL defects.The average intraocular pressure (IOP) measured from 3 separate visits within 6 months was 24.9 ± 1.8 mmHg for the eye with higher IOP and 23.7 ± 1.7 mmHg for the eye with lower IOP; the respective central corneal thicknesses were 568.7 ± 30.8 μm and 568.8 ± 31.2 μm. Of 306 patients with OHT, 10.8% (33 patients, 37 eyes) demonstrated RNFL defects in ROTA in at least 1 eye. Of the 37 eyes with RNFL defects, the superior arcuate bundle was the most frequently involved (62.2%), followed by the superior papillomacular bundle (27.0%) and the inferior papillomacular bundle (21.6%). Papillofoveal bundle defects were observed in 10.8% of eyes. The smallest RNFL defect spanned 0.0° along Bruch's membrane opening margin, whereas the widest RNFL defect extended over 29.3°. Age (years) (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.03-1.13), VF pattern standard deviation (decibels [dB]) (OR, 1.82; 95% CI, 1.01-3.29), cup volume (mm3) (OR, 1.24; 95% CI, 1.01-1.53), and the OHTS-EPGS risk score (OR, 1.04; 95% CI, 1.01-1.07) were associated with RNFL defects.A considerable proportion of patients with OHT who showed no signs of optic disc and RNFL thickness abnormalities on clinical and OCT examination exhibited RNFL defects on ROTA. Axonal fiber bundle defects on ROTA may represent the earliest discernible sign of glaucoma in the glaucoma continuum.Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Brain responses to nutrients are severely impaired and not reversed by weight loss in humans with obesity: a randomized crossover study
Authors: Katy A. van Galen, Anouk Schrantee, Kasper W. ter Horst, Susanne E. la Fleur, Jan Booij, R. Todd Constable, Gary J. Schwartz, Ralph J. DiLeone, Mireille J. Serlie
Journal: Nature Metabolism (2023)
A rapid and bidirectional reporter of neural activity reveals neural correlates of social behaviors in Drosophila
Authors: Moise Bonheur, Kurtis J. Swartz, Melissa G. Metcalf, Xinke Wen, Anna Zhukovskaya, Avirut Mehta, Kristin E. Connors, Julia G. Barasch, Andrew R. Jamieson, Kelsey C. Martin, Richard Axel, Daisuke Hattori
Journal: Nature Neuroscience (2023)
Chromatin reprogramming and bone regeneration in vitro and in vivo via the microtopography-induced constriction of cell nuclei
Authors: Xinlong Wang, Vasundhara Agrawal, Cody L. Dunton, Yugang Liu, Ranya K. A. Virk, Priyam A. Patel, Lucas Carter, Emily M. Pujadas, Yue Li, Surbhi Jain, Hao Wang, Na Ni, Hsiu-Ming Tsai, Nancy Rivera-Bolanos, Jane Frederick, Eric Roth, Reiner Bleher, Chongwen Duan, Panagiotis Ntziachristos, Tong Chuan He, Russell R. Reid, Bin Jiang, Hariharan Subramanian, Vadim Backman, Guillermo A. Ameer
Journal: Nature Biomedical Engineering (2023)
The colonial legacy of herbaria
Authors: Daniel S. Park, Xiao Feng, Shinobu Akiyama, Marlina Ardiyani, Neida Avendaño, Zoltan Barina, Blandine Bärtschi, Manuel Belgrano, Julio Betancur, Roxali Bijmoer, Ann Bogaerts, Asunción Cano, Jiří Danihelka, Arti Garg, David E. Giblin, Rajib Gogoi, Alessia Guggisberg, Marko Hyvärinen, Shelley A. James, Ramagwai J. Sebola, Tomoyuki Katagiri, Jonathan A. Kennedy, Tojibaev Sh. Komil, Byoungyoon Lee, Serena M. L. Lee, Donatella Magri, Rossella Marcucci, Siro Masinde, Denis Melnikov, Patrik Mráz, Wieslaw Mulenko, Paul Musili, Geoffrey Mwachala, Burrell E. Nelson, Christine Niezgoda, Carla Novoa Sepúlveda, Sylvia Orli, Alan Paton, Serge Payette, Kent D. Perkins, Maria Jimena Ponce, Heimo Rainer, L. Rasingam, Himmah Rustiami, Natalia M. Shiyan, Charlotte Sletten Bjorå, James Solomon, Fred Stauffer, Alex Sumadijaya, Mélanie Thiébaut, Barbara M. Thiers, Hiromi Tsubota, Alison Vaughan, Risto Virtanen, Timothy J. S. Whitfeld, Dianxiang Zhang, Fernando O. Zuloaga, Charles C. Davis
Journal: Nature Human Behaviour (2023)
Two cases of severe pulmonary toxicity from highly active mesothelin-directed CAR T cells
Authors: Andrew R. Haas, Ryan J. Golden, Leslie A. Litzky, Boris Engels, Linlin Zhao, Fangmin Xu, John A. Taraszka, Melissa Ramones, Brian Granda, Wan-Jung Chang, Julie Jadlowsky, Kim-Marie Shea, Adam Runkle, Anne Chew, Emily Dowd, Vanessa Gonzalez, Fang Chen, Xiaojun Liu, Chongyun Fang, Shuguang Jiang, Megan M. Davis, Neil C. Sheppard, Yangbing Zhao, Joseph A. Fraietta, Simon F. Lacey, Gabriela Plesa, J. Joseph Melenhorst, Keith Mansfield, Jennifer L. Brogdon, Regina M. Young, Steven M. Albelda, Carl H. June, Janos L. Tanyi
Journal: Molecular Therapy (2023)
A chimeric human/dog-DNA vaccine against CSPG4 induces immunity with therapeutic potential in comparative preclinical models of osteosarcoma
Authors: Lidia Tarone, Davide Giacobino, Mariateresa Camerino, Lorella Maniscalco, Selina Iussich, Lorenza Parisi, Giuseppe Giovannini, Alfredo Dentini, Elisabetta Bolli, Elena Quaglino, Irene Fiore Merighi, Emanuela Morello, Paolo Buracco, Federica Riccardo, Federica Cavallo
Journal: Molecular Therapy (2023)

The high mortality rate of osteosarcoma (OSA) patients highlights the requirement of alternative strategies. The young age of patients, as well as the rarity and aggressiveness of the disease, limits opportunities for the robust testing of novel therapies, suggesting the need for valuable preclinical systems. Having previously shown the overexpression of the chondroitin sulfate proteoglycan (CSPG)4 in OSA, herein the functional consequences of its downmodulation in human OSA cells were evaluated in vitro, with a significant impairment of cell proliferation, migration, and osteosphere generation. The potential of a chimeric human/dog (HuDo)-CSPG4 DNA vaccine was explored in translational comparative OSA models, including human xenograft mouse models and canine patients affected by spontaneous OSA. The adoptive transfer of HuDo-CSPG4 vaccine-induced CD8
OCTN2 enhances PGC-1α-mediated fatty acid oxidation and OXPHOS to support stemness in hepatocellular carcinoma
Authors: Tao Yang, Ning Liang, Jiahao Zhang, Yaxing Bai, Yuedan Li, Zifeng Zhao, Liusheng Chen, Min Yang, Qian Huang, Pan Hu, Qian Wang, Hongxin Zhang
Journal: Metabolism (2023)
Single cell clonotypic and transcriptional evolution of multiple myeloma precursor disease
Authors: Minghao Dang, Guangchun Han, Hans C. Lee, Krina K. Patel, Melody R. Becnel, Ruiping Wang, Sheeba K. Thomas, Dapeng Hao, Yanshuo Chu, Donna M. Weber, Pei Lin, Zuzana Lutter-Berka, David A. Berrios Nolasco, Mei Huang, Hima Bansal, Xingzhi Song, Jianhua Zhang, Andrew Futreal, Luz Yurany Moreno Rueda, David E. Symer, Michael R. Green, Cristhiam M. Rojas Hernandez, Michael Kroll, Vahid Afshar-Khargan, Libere J. Ndacayisaba, Peter Kuhn, Sattva S. Neelapu, Robert Z. Orlowski, Linghua Wang, Elisabet E. Manasanch
Journal: Cancer Cell (2023)
Taxanes trigger cancer cell killing in vivo by inducing non-canonical T cell cytotoxicity
Authors: Claire Vennin, Chiara M. Cattaneo, Leontien Bosch, Serena Vegna, Xuhui Ma, Hugo G.J. Damstra, Moreno Martinovic, Efi Tsouri, Mila Ilic, Leyla Azarang, Jan R.T. van Weering, Emilia Pulver, Amber L. Zeeman, Tim Schelfhorst, Jeroen O. Lohuis, Anne C. Rios, Johanna F. Dekkers, Leila Akkari, Renee Menezes, Rene Medema, Serena R. Baglio, Anna Akhmanova, Sabine C. Linn, Simone Lemeer, Dirk M. Pegtel, Emile E. Voest, Jacco van Rheenen
Journal: Cancer Cell (2023)

Although treatment with taxanes does not always lead to clinical benefit, all patients are at risk of their detrimental side effects such as peripheral neuropathy. Understanding the in vivo mode of action of taxanes can help design improved treatment regimens. Here, we demonstrate that in vivo, taxanes directly trigger T cells to selectively kill cancer cells in a non-canonical, T cell receptor-independent manner. Mechanistically, taxanes induce T cells to release cytotoxic extracellular vesicles, which lead to apoptosis specifically in tumor cells while leaving healthy epithelial cells intact. We exploit these findings to develop an effective therapeutic approach, based on transfer of T cells pre-treated with taxanes ex vivo, thereby avoiding toxicity of systemic treatment. Our study reveals a different in vivo mode of action of one of the most commonly used chemotherapies, and opens avenues to harness T cell-dependent anti-tumor effects of taxanes while avoiding systemic toxicity.
Adiposity and sex-specific cancer risk
Authors: Mathias Rask-Andersen, Emma Ivansson, Julia Höglund, Weronica E. Ek, Torgny Karlsson, Åsa Johansson
Journal: Cancer Cell (2023)

Obesity is associated with several types of cancer and fat distribution, which differs dramatically between sexes, has been suggested to be an independent risk factor. However, sex-specific effects on cancer risk have rarely been studied. Here we estimate the effects of fat accumulation and distribution on cancer risk in females and males. We performed a prospective study in 442,519 UK Biobank participants, for 19 cancer types and additional histological subtypes, with a mean follow-up time of 13.4 years. Cox proportional hazard models were used to estimate the effect of 14 different adiposity phenotypes on cancer rates, and a 5% false discovery rate was considered statistically significant. Adiposity-related traits are associated with all but three cancer types, and fat accumulation is associated with a larger number of cancers compared to fat distribution. In addition, fat accumulation or distribution exhibit differential effects between sexes on colorectal, esophageal, and liver cancer.
6-month consequences of COVID-19 in patients discharged from hospital: a cohort study
Authors: Chaolin Huang, Lixue Huang, Yeming Wang, Xia Li, Lili Ren, Xiaoying Gu, Liang Kang, Li Guo, Min Liu, Xing Zhou, Jianfeng Luo, Zhenghui Huang, Shengjin Tu, Yue Zhao, Li Chen, Decui Xu, Yanping Li, Caihong Li, Lu Peng, Yong Li, Wuxiang Xie, Dan Cui, Lianhan Shang, Guohui Fan, Jiuyang Xu, Geng Wang, Ying Wang, Jingchuan Zhong, Chen Wang, Jianwei Wang, Dingyu Zhang, Bin Cao
Journal: The Lancet (2023)
The legacy effect of hyperglycemia and early use of SGLT-2 inhibitors: a cohort study with newly-diagnosed people with type 2 diabetes
Authors: Antonio Ceriello, Giuseppe Lucisano, Francesco Prattichizzo, Rosalba La Grotta, Chiara Frigé, Salvatore De Cosmo, Paolo Di Bartolo, Graziano Di Cianni, Paola Fioretto, Carlo Bruno Giorda, Roberto Pontremoli, Giuseppina Russo, Francesca Viazzi, Antonio Nicolucci
Journal: The Lancet Regional Health - Europe (2023)

A delay in reaching HbA1c targets in patients with newly-diagnosed type 2 diabetes (T2D) is associated with an increased long-term risk of developing cardiovascular diseases (CVD), a phenomenon referred to as legacy effect. Whether an early introduction of glucose-lowering drugs with proven benefit on CVD can attenuate this phenomenon is unknown. Using data derived from a large Italian clinical registry, i.e. the AMD Annals, we identified 251,339 subjects with newly-diagnosed T2D and without CVD at baseline. Through Cox regressions adjusted for multiple risk factors, we examined the association between having a mean HbA1c between 7.1 and 8% or >8%, compared with ≤7%, for various periods of early exposure (0–1, 0–2, 0–3 years) and the development of later (mean subsequent follow-up 4.6 ± 2.9 years) CVD, evaluated as a composite of myocardial infarction, stroke, coronary or peripheral revascularization, and coronary or peripheral bypass. We performed this analysis in the overall cohort and then splitting the population in two groups of patients: those that introduced sodium-glucose transport protein 2 inhibitors (SGLT-2i) during the exposure phase and those not treated with these drugs. Considering the whole cohort, subjects with both a mean HbA1c between 7.1 and 8% and >8%, compared with patients attaining a mean HbA1c ≤ 7%, showed an increased risk of developing the outcome in all the three early exposure periods assessed, with the highest risk observed in patients with mean HbA1c > 8% in the 3 years exposure period (hazard ratio [HR]1.33; 95% confidence interval [CI] 1.063–1.365). The introduction of SGLT-2i during the exposure periods of 0–1 and 0–2 years eliminated the association between poor glycemic control and the outcome (p for interaction 0.006 and 0.003, respectively, vs. patients with the same degree of glycemic control but not treated with these drugs). Among patients with newly diagnosed T2D and free of CVD at baseline, a poor glycemic control in the first three years after diagnosis is associated with an increased subsequent risk of CVD. This association is no longer evident when SGLT-2i are introduced in the first two years, suggesting that these drugs attenuate the phenomenon of legacy effect. An early treatment with these drugs might thus promote a long-lasting benefit in patients not attaining proper glycemic control after T2D diagnosis. This work was supported, in part, by the Italian Ministry of Health (Ricerca Corrente) to IRCCS MultiMedica.